DESCRIPTION: Lung leaks from surgery, injury or diseases may result in lung collapse, which can be immediately life threatening. Treating a collapsed lung begins with emergent placement of a chest tube into the pleural space so that the accumulated air or liquid can be evacuated in order to re-inflate the lung. However, collapse often occurs in the setting of poorly healing tissue. Extensive tissue damage and chronic leak lead to substantial morbidity, mortality, and correspondingly high health care costs. To address these challenges, the proposed research will explore the use of a natural material, alginate, for use as a tissue sealant and therapeutic patch, to effectively treat lung leaks and aid in lung tissue regeneration. Chemically modified alginate, methacrylated alginate (Alg-MA), will be further modified to enhance adhesion to the lung surface to form a better seal. The use of the hydrogel as a drug carrier is also proposed to enhance wound healing. The overarching goal of our application is thus to establish the potential clinical efficacy of Alg- MA hydrogels as combination pleural sealants and therapeutic patches. The experimental design is centered on three aims: 1) to determine how the physical properties of Alg-MA hydrogels impact their capacity to seal a pleural leak, 2) to determine how Alg-MA hydrogel properties affect their capacity for dynamic mechanical stability and controlled release of drugs, and 3) to assess the ability of drug-eluting Alg-MA hydrogels to repair damaged pleural tissue in vivo. Alg-MA materials will be oxidized to enhance tissue adhesion, thus improving the burst pressure and sealant properties of the material. In addition, blending of Alg-MA with a similar natural material, hyaluronan (HA) will enhance the dynamic mechanical properties to ensure dynamic durability and longevity of leak prevention in vivo. To characterize the long-term use of the hydrogel sealant, adhesion and mechanical properties will be tailored to enhance degradation properties and drug release rates. An in vivo rodent model will be used to evaluate the efficacy of Alg-MA hydrogels as durable sealants and carriers for therapeutic drugs. Indeed, the broader impact of the proposed research is the development of a medical sealant for various uses, especially in cases when selective tissue adhesion is desired.